Our immunocytochemical studies on normal human colonic epithelium have demonstrated that two glycoproteins on the cell surfaces are distributed in a polar manner: Secretory component (SC), the membrane receptor for polymeric immunoglobulins, is located exclusively on the apical membrane. In colonic adenocarcinoma, SC is reduced in amount or absent, and CEA is expressed over the entire cell surface. We propose to examine further the biological and therapeutic implications of disturbances in the polar distribution of membrane surface antigens. The specific aims are: (1) Determine the specificity and extent of alterations in cell surface markers in neoplastic and inflammatory diseases of the large bowel and other organs. Various epithelial tumors and tissues from inflammatory bowel diseases will be examined for distributional changes in CEA and SC as well as in enzyme markers (alkaline phosphatase and K ion-dependent phosphatase) of the cell surface domains. (2) Produce an animal model for study of the abnormal distribution of surface membrane components in neoplastic transformation of colon epithelial cells. Two markers of the basolateral membranes of rat colon epithelial cells (SC and K ion-dependent phosphatase) and two markers of the apical membrane (alkaline phosphatase and an immunocytochemically indentifiable marker) will be localized. Alterations in surface distribution of the membrane markers during neoplastic transformation induced by dimethylhydrazine will be monitored. (3) Utilize redistributed surface membrane components in the therapy of experimentally induced colonic cancers. Colonic tumors will be induced in rats by dimethylhydrazine, and an attempt will be made to destroy the tumor cells by injected heteroantibodies directed specifically against apical membrane components aberrantly expressed on basolateral surfaces.